Concurrent micro- to macro-cardiac electrophysiology in myocyte cultures and human heart slices

Chowdhury, Rasheda A.; Tzortzis, Konstantinos N.; Dupont, Emmanuel; Selvadurai, Shaun; Perbellini, Filippo; Cantwell, Chris D.; Ng, Fu Siong; Simón, A.; Terracciano, Cesare M.; Peters, Nicholas S.

doi:10.1038/s41598-018-25170-9

Cited by 24 publications

(20 citation statements)

References 44 publications

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“…Fractionation is a feature of the electrogram which is measured clinically [20] and is thought to be associated with cell-to-cell discontinuity. Therefore, it is unsurprising that cellular uncoupling leads to an increase in fractionation, and is consistent with our previous findings [4]. We have identified further features of the electrogram not previously associated with cellular uncoupling.…”

Section: Feature Analysissupporting

confidence: 93%

“…We have previously used pharmacological modulators in simpler tissue and cell models to demonstrate modifications to ion channels and cellular coupling can be interpreted in the EGM [4]. Investigating these abnormalities in ex vivo intact hearts may provide insight into arrhythmogenic mechanisms.…”

Section: Pharmacological Modulationmentioning

confidence: 99%

“…Our Langendorff apparatus can be used to administer other pharmacological modulators to investigate other arrhythmogenic substrates, such as ion channel blockers [4]. Identifying the features with most significant changes from BL in these EGMs could be used to establish collectively which combination of features differentiate between normal and different specific pathological EGMs, leading to a greater understanding of how pathological myocardial electrophysiological function manifests in the clinically accessible EGM.…”

Section: Feature Analysismentioning

confidence: 99%

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Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling

Brook

Kim

Koutsoftidis

et al. 2020

Pflugers Arch - Eur J Physiol

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We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting. Porcine (n = 9) and human (n = 4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. A total of 1 mM of carbenoxolone was administered at 5 ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed. We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9 ± 4.1–67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and carbenoxolone were fractionation + 185.3%, endpoint amplitude − 106.9%, S-endpoint gradient + 54.9%, S point − 39.4%, RS ratio + 38.6% and (-dV/dt)max − 20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates.

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Section: Feature Analysissupporting

confidence: 93%

Section: Pharmacological Modulationmentioning

confidence: 99%

Section: Feature Analysismentioning

confidence: 99%

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Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling

Brook

Kim

Koutsoftidis

et al. 2020

Pflugers Arch - Eur J Physiol

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“…Chowdhury et al considered that the contact electrogram is related with cellular action potential and should change in conjunction with each other during arrhythmogenesis. They developed a novel technique combining MEA recordings with optical mapping to simultaneously record the contact electrograms and action potentials [60]. Also, biomechanical measurements on cardiomyocytes for investigating the pathophysiological electro-mechanical coupling were done by using the stretcher device previously [61].…”

Section: Biosensors For Cell Behaviors Such As Metabolism the Prolifmentioning

confidence: 99%

The Current Trends of Biosensors in Tissue Engineering

Lee

2020

Biosensors

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Biosensors constitute selective, sensitive, and rapid tools for disease diagnosis in tissue engineering applications. Compared to standard enzyme-linked immunosorbent assay (ELISA) analytical technology, biosensors provide a strategy to real-time and on-site monitor micro biophysiological signals via a combination of biological, chemical, and physical technologies. This review summarizes the recent and significant advances made in various biosensor technologies for different applications of biological and biomedical interest, especially on tissue engineering applications. Different fabrication techniques utilized for tissue engineering purposes, such as computer numeric control (CNC), photolithographic, casting, and 3D printing technologies are also discussed. Key developments in the cell/tissue-based biosensors, biomolecular sensing strategies, and the expansion of several biochip approaches such as organs-on-chips, paper based-biochips, and flexible biosensors are available. Cell polarity and cell behaviors such as proliferation, differentiation, stimulation response, and metabolism detection are included. Biosensors for diagnosing tissue disease modes such as brain, heart, lung, and liver systems and for bioimaging are discussed. Finally, we discuss the challenges faced by current biosensing techniques and highlight future prospects of biosensors for tissue engineering applications.

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“…Electrogram recordings were acquired as previously described [49]. In brief, cell monolayers of neonatal rat ventricular myocytes (NRVMs) were seeded onto five microelectrode arrays (MEA), each consisting of 60 electrodes (MultiChannel Systems, Reutlingen, Germany).…”

Section: Data Acquisition and Pre-processingmentioning

confidence: 99%

Rethinking multiscale cardiac electrophysiology with machine learning and predictive modelling

Cantwell

Mohamied

Tzortzis

et al. 2019

Computers in Biology and Medicine

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We review some of the latest approaches to analysing cardiac electrophysiology data using machine learning and predictive modelling. Cardiac arrhythmias, particularly atrial fibrillation, are a major global healthcare challenge. Treatment is often through catheter ablation, which involves the targeted localised destruction of regions of the myocardium responsible for initiating or perpetuating the arrhythmia. Ablation targets are either anatomically defined, or identified based on their functional properties as determined through the analysis of contact intracardiac electrograms acquired with increasing spatial density by modern electroanatomic mapping systems. While numerous quantitative approaches have been investigated over the past decades for identifying these critical curative sites, few have provided a reliable and reproducible advance in success rates. Machine learning techniques, including recent deep-learning approaches, offer a potential route to gaining new insight from this wealth of highly complex spatio-temporal information that existing methods struggle to analyse. Coupled with predictive modelling, these techniques offer exciting opportunities to advance the field and produce more accurate diagnoses and robust personalised treatment. We outline some of these methods and illustrate their use in making predictions from the contact electrogram and augmenting predictive modelling tools, both by more rapidly predicting future states of the system and by inferring the parameters of these models from experimental observations.

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Concurrent micro- to macro-cardiac electrophysiology in myocyte cultures and human heart slices

Cited by 24 publications

References 44 publications

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling

The Current Trends of Biosensors in Tissue Engineering

Rethinking multiscale cardiac electrophysiology with machine learning and predictive modelling

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